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Thursday, January 31, 2008
Deep Research
Molecular Information Theory
The Work of Dr. Tom Schneider from the NCIFCRF deserves it's own special section. While Shannon Entropy has been applied in InfoTech and communications for decades, it is relatively unknown amongst today's medical researchers. This field, known as "Molecular Information Theory" is not only key to the next generation of medicine, it is very important to the field of nano-engineering and molecular machines.
- An important warning on the distinction between Thermodynamic Entropy and Shannon Entopy.
- A good primer for biologists unfamiliar with Claude Shannon's Information Theory.
- A good start for computer science people is this article on Claude Shannon and Biology. pdf full cite
- This advanced article discusses molecular machines in depth using Molecular Info Theory. pdf full cite
- Complete tour of Molecular Information Theory with above articles and more.
- Dr. Schneider's comprehensive home page is found here.
Systems Theory
Systems Theory has deep history in computer science and its application has been around for decades with such technologies as Object Oriented Programming and Dsitributed Computing. There has been work going on to apply this mature science to medicine. Indeed, the health care crisis will not be resolved until reductionism is replaced with this new (to biology and medicine) paradigm. Many InfoTech people have a difficult time accepting that Systems Theory is largely new to medicine. So, really, let me underscore the point to be prefectly clear. This paradigm is largely obscure to practicing physicians and pharmaceutical researchers. Really.
- Self-organization, Emergence and the Architecture of Complexity
This article is pretty deep, but comprehensible for anyone that has ever designed or programmed an object oriented system. A good bit of math is discussed, but no Greek letters. It does an excellent job of explaining how system becomes emergent. The full cite is below. I highly recommend it to both InfoTech people and open minded Molecular Biologists looking for a deep conceptual explanation of Systems Theory.
Heylighen F. (1989): "Self-Organization, Emergence and the Architecture of Complexity", in:
Proceedings of the 1st European Conference on System Science, (AFCET, Paris), p. 23-32.
Emergence Versus Self-Organisation:
Different Concepts but Promising When Combined
Tom De Wolf and Tom Holvoet
Department of Computer Science, Kuleuven,
Celestijnenlaan 200A, 3001 Leuven, Belgium
{Tom.DeWolf, Tom.Holvoet}@cs.kuleuven.ac.be
This article makes some extremely important points about the history of complexity science and the meanings of key terms. These definitions are important indeed to keep straight.- Here is a link to Tom De Wolf's full bibliography of very useful work.
Books
This section contains reviews of books related to technology, systems, medical reform, and health.
The End of Medicine. Andy Kessler.
Andy is a Silicon Valley entrepreneur and VC with much success to his credit. His very readable book details how imaging and diagnostics will bring scale, efficiency, and automation to medicine. Best vision that I’ve seen so far, although he only mentions systems in passing.
Introduction to Systems Biology. Dr. Uri Alon.
This book is by far the simplest and most straight forward. Dr. Alon understands the notion of patterns (motifs) that make complex systems simpler. Indeed, his book is the closest to the “Gang of four” pattern book that every OO programmer has on his desk. Not there yet, as Dr. Alon acknowledges, but a really excellent start.
Systems Biology: Properties of Reconstructed Networks. Bernhard O. Palsson.
Palsson does an excellent job at providing historical context for SB and calls for the establishment of standards. He should also be congratulated for calling for an effort to map the hierarchy of the system—its “Enterprise Architecture” if you will. On the down side, he misses a fundamental point on page 23: the amino acid code is not random, but rather, it is optimized for the laws of Shannon Entropy. Also, he is still reluctant to recognize that the system is “designed” to insulate itself from stochastic effects associated with thermodynamics. He emphasizes that the system is “constrained” by the laws of chemistry. Not a useful way to look at it. He also engages in endless arbitrarily complex math regarding optimal states. A dressmaker just uses the pattern book because the patterns are useful. She doesn’t whip out any differential equations to prove it.
Design Patterns: Elements of Reusable Object-Oriented Software.
Erich Gamma, Richard Helm, Ralph Johnson, John M. Vlissides
This book is better known for its authors, the “Gang of four”. If you’ve ever designed software you’ve seen this book. Ultimately, this book has to cover everything in carbon-based systems, too. It has to do with Information entropy. I don’t think that the biologists are generally hip to this fact yet.
Health Care Public Policy
This page contains links to articles, research papers, and blog entries regarding issues of public policy and controversial health practices.
- This paper published at the CHCF site chronicles the truly disturbing delays and negative attitudes of physicians in adopting urgent reforms. Indeed, our health care delivery system seems to be 15 years behind corporate America in understanding the fundamental truth of change. If you can't change the people, you have to change the people.
The Science of Spread: How Innovations in Care Become the Norm - This article from Yahoo! is crucial to understanding how new medical technology will sharply reduce spending on diabetes and on chronic care in general. Indeed, along with Cancer, heart disease and stroke, diabetes is one of the four top line items in our health care budget. It would be nice if individuals had more help in managing diet and exercise, but our current paradigm is about letting things break. With alternatives like this one for treating obesity, we get the benefits of improved health and reduced cost. Andy Kessler makes this point in his book: "The End of Medicine".
Obesity surgery seen as diabetes cure - This page from the NY Times chronicles the controversy regarding the epidemic of doctors diagnosing young children with bi-polar disorder and treating them with regimens of powerful drugs.
Troubled Children: A Series
Grass Roots Medical Reform
This page contains links demonstrating that concerned individuals are finding ways to bypass medical bureaucracy and offer creative solutions for developing medical breakthroughs.
- This article is a good example of how individuals who are diagnosed with life threatening illnesses often find that they are going up against a system that hinders innovation.
Lab Rat?WSJ - I found this article to be enlightening and disturbing at the same time. I see this effort as a good first start to forcing medicine to become more responsive to patients and society. A little entrepreneurship and cooperation never hurt. What is disturbing is that with all the good ideas submitted, the doctors interviewed were skeptical that there could be any good ideas out there that doctors weren't already working on. I guess the guy slept through math class when they discussed Godel's Incompleteness Theorem. Or perhaps he feels that God made special exceptions for doctors that allow them to be all knowing and infallible. Perhaps the guy could check out this site for a few "New" ideas for medicine, like the ones that are in the process of revolutionizing it.
Will Sharing Ideas Advance Cancer Research?WSJ - This blog entry reviews an article discussing new legislation forcing researchers using public dollars to make their research available to the public.
Wednesday, January 30, 2008
Pharm and BioTech News
- Systems Biology’s Awkward Adolescence BioITWorld
- Bush plan would allow generic biotech drugs Chicago Tribune
Academic Research Paper Links
Reductionism and complexity in molecular biology.
This article is a great place for the mildly-scientifically inclined to get started in understanding the challenges with our current medical paradigm. It does a good job of defining reductionism, and why it has limitations in a clear manner with specific examples. It is also blissfully free of Greek letters, strange mathematical symbols, and generally incomprehensible jargon. The author does an excellent job of making the provocative assertion that effort spent on HIV vaccine development has been hindered by reductionism.
Van Regenmortel M.H.V. 2004. Reductionism and complexity in molecular biology. EMBO Reports 5, 1016-1020.
Tuesday, January 29, 2008
The Nano Bubble Blog Rant
Silicon Valley IT companies will accelerate the convergence between Life Sciences and Computer Science in 2008 and beyond. This convergence will ultimately lead to the dis-intermediation of the entrenched pharmaceutical and health care industries and their political lobbies. Ten years from today, most of the diagnosis and treatment decisions currently performed by doctors will be automated. Obsolescence for existing doctors and medical students may be near. At the same time, consumers will make their own decisions based on facts, not physician opinions. Not only will consumers enjoy better health for dramatically lowered costs, they will remove an undemocratic element from our society.
Few realize that roughly half of the 50 United States, including California, allow physicians to make decisions for their patients without fully informing them of risks and alternatives. In the same way, the American Medical Association has placed the blame for our health care crisis on insurance companies while neglecting to mention that our medical and pharmaceutical paradigm is based on junk science that is mathematically impossible. As a result of this lack of disclosure, taxpayers are forced to fund expensive research that has no basis in science, throwing even more good money after bad. Ultimately, taxpayers have no say in stopping the AMA, Universities, and health care providers from wasting their money. The only democratic scrutiny in our medical system is our Byzantine tort system, resulting in the worst outcomes for everyone.
Many BioTech CEOs have long believed that IT people would leverage the valley's continuing education infrastructure to launch new careers in BioTech. Instead, they represent the tip of a wedge that will turn the BioTech Industry upside down. Silicon Valley engineers are learning that the current paradigm must be replaced with computer science based methods. Many of today’s pharmaceutical companies will write-off multi-billion dollar pipelines, or face the wrath of the tort industry. What remains to be seen is whether the CEOs and shareholders will be forced to swallow the loss, or whether we all have to continue to pay for dangerous, ineffective, and toxic drugs through our Medicaid and Medicare dollars. A new industry and a new way of doing business will arise out of the ashes of the old BioTech and Big Pharm model.
Awareness that biological information systems and human designed IT systems converge on the same design principles is increasingly reaching IT executives and VCs. Silicon Valley will pounce on the opportunity to get in on the bonanza. A new tech boom will result as the valley re-deploys existing talent to develop and patent models of biological pathways that will then be licensed to create “System-designed” diagnostics and drugs. Next generation companies will cooperate through open source consortia, forcing pharmaceutical and university researchers to change or face extinction. In addition to the promise of lower health care costs, IT companies will be motivated to participate in open source medical research by the need to acquire new engineering skills. IT companies will learn how to revolutionize their own core markets with nano-based technologies. Health care will become digital, democratized, ubiquitous and cheap. An entirely new product-oriented health care paradigm will displace the existing people and players and create new fortunes for entrepreneurs and savvy executives. Those individuals and companies that successfully make the transition will enjoy unprecedented opportunities for achievement and wealth.
Medicine is Based on Outdated Science
Today, drug development and physician practices are based on the belief that a system is nothing more than the sum of its parts studied in isolation. This ideology is called "Reductionism". According to Doctors and Bio-Chemists, living systems are the products of chemical reactions and nothing more. Based on the laws of chemistry and nothing more, doctors and researchers believe that they can understand a system "bottoms up". Our tax dollars and insurance premiums go to the private and academic medical complex based on these beliefs. The trouble is that science has known that this belief is not mathematically sound since 1931 when Kurt Godel published his Incompleteness Theorem.
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